The Right Therapy for Neurological Disorders

Description

Most neurological disorders are chronic and aging-related. With the increase of life expectancy their incidence and prevalence will grow in the decades to come, which in turn will increase the load on medical and social systems worldwide. There is thus a desperate need for successful preventive and therapeutic measures based on randomized clinical trials (RTCs) conducted by independent organizations. This book provides a compendium relating most of the principles of reliable RTCs to specific neurological diseases. Contributed by specialized neurologists, the articles touch on important aspects of RCTs with a clear critical approach, highlighting their limitations as well as giving recommendations for their planning and conducting to address the variable genotypic and phenotypic aspects of neurological conditions. Consideration is also given to combining the clinical impact of the study results with patients’ values and the interests of pharmaceutical companies. Neurologists involved in clinical trials will certainly benefit from this book, which should become a basic text for all neurological courses dealing with evidence-based neurology.

Informations

• Publié par: S. Karger AG
• Date de parution: 26 juillet 2016
• Nombre de lectures: 0
• EAN13: 9783318058659
• Langue: English
• Poids de l'ouvrage: 1 Mo

Extrait

The Right Therapy for Neurological Disorders
Frontiers of Neurology and Neuroscience
Vol. 39
Series Editor
J. Bogousslavsky Montreux
The Right Therapy for Neurological Disorders
From Randomized Trials to Clinical Practice
Volume Editors
E. Beghi Milan
G. Logroscino Bari/Tricase
18 figures, 1 in color, and 16 tables, 2016
Frontiers of Neurology and Neuroscience Vols. 1-18 were published as Monographs in Clinical Neuroscience
_______________________ Ettore Beghi, MD Laboratory of Neurological Disorders ICRRS - Mario Negri Institute for Pharmacological Research IT-20156 Milan (Itlay)
_______________________ Giancarlo Logroscino, MD Unit of Neurodegenerative Diseases Department of Clinical Research in Neurology University of Bari ‘Aldo Moro’ ‘Pia, Fondazione Cardinale G. Panico’ IT-73039 Tricase (Italy)
Library of Congress Cataloging-in-Publication Data
Names: Beghi, E. (Ettore), editor. | Logroscino, G. (Giancarlo), editor.
Title: The right therapy for neurological disorders : from randomized trials to clinical practice / volume editors, E. Beghi, G. Logroscino.
Other titles: Frontiers of neurology and neuroscience ; v. 39. 1660-4431
Description: Basel ; New York : Karger, 2016. | Series: Frontiers of neurology and neuroscience, ISSN 1660-4431 ; vol. 39 | Includes bibliographical references and indexes.
Identifiers: LCCN 2016019282| ISBN 9783318058642 (hard cover : alk. paper) | ISBN 9783318058659 (e-ISBN)
Subjects: | MESH: Nervous System Diseases--drug therapy | Randomized Controlled Trials as Topic | Drug Evaluation--methods | Treatment Outcome | Evidence-Based Medicine--methods
Classification: LCC RM315 | NLM WL 140 | DDC 616.8/0461--dc23 LC record available at https://lccn.loc.gov/2016019282

Bibliographic Indices. This publication is listed in bibliographic services, including Current Contents ® and Index Medicus.
Disclaimer. The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publisher and the editor(s). The appearance of advertisements in the book is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
Drug Dosage. The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any change in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
© Copyright 2016 by S. Karger AG, P.O. Box, CH-4009 Basel (Switzerland)
www.karger.com
Printed on acid-free and non-aging paper (ISO 9706)
ISSN 1660-4431
e-ISSN 1662-2804
ISBN 978-3-318-05864-2
e-ISBN 978-3-318-05865-9
Contents
Foreword
Garattini, S. (Milan)
Preface
Beghi, E. (Milan); Logroscino, G. (Bari/Tricase)
The Basic Structure of a Randomized Clinical Trial
Beghi, E. (Milan)
Peculiarities of Neurological Disorders and Study Designs
Beghi, E.; Pupillo, E.; Giussani, G. (Milan)
Current Issues in Randomized Clinical Trials of Neurodegenerative Disorders at Enrolment and Reporting: Diagnosis, Recruitment, Representativeness of Patients, Ethnicity, and Quality of Reporting
Logroscino, G.; Capozzo, R.; Tortelli, R. (Bari/Tricase); Marin, B. (Bari/Tricase/Limoges)
How to Distinguish between Statistically Significant Results and Clinically Relevant Results
Bennett, D.A. (Oxford)
Modeling and Prediction in Neurological Disorders: The Biostatistical Perspective
Copetti, M.; Fontana, A. (San Giovanni Rotondo); Pellegrini, F. (Cambridge, Mass.)
Composite Scores and Other Outcome Measures in Stroke Trials
Pistoia, F.; Sacco, S.; Ornello, R.; Degan, D.; Tiseo, C.; Carolei, A. (L'Aquila)
Age, Comorbidity, Frailty in Observational and Analytic Studies of Neurological Diseases
Novy, J. (Lausanne); Sander, J.W. (London/Chalfont St. Peter/Heemstede)
Disease Course, Outcome Measures, and Prognostic Predictors in Epilepsy: Opportunities for Improving Outcome of Drug Trials
Schmidt, D. (Berlin)
Assessing Functional Decline in Neurological Diseases Clinical Trials: Duration of Follow-Up - The Case of Multiple Sclerosis
Martinelli Boneschi, F.; Comi, G. (Milan)
Biomarkers in Randomized Clinical Trials: Magnetic Resonance Imaging
Whitwell, J.L. (Rochester, Minn.)
Biomarkers in Randomized Clinical Trials: Positron Emission Tomography and Nuclear Medicine Techniques
Singhal, T.; Stern, E. (Boston, Mass.)
Cerebrospinal Fluid Biomarkers for Target Engagement and Efficacy in Clinical Trials for Alzheimer's and Parkinson's Diseases
Parnetti, L.; Eusebi, P. (Perugia); Lleó, A. (Barcelona/Madrid)
Pharmacogenetics in Neurodegenerative Diseases: Implications for Clinical Trials
Tortelli, R. (Bari/Tricase); Seripa, D. (San Giovanni Rotondo);
Panza, F. (Bari/Tricase/San Giovanni Rotondo); Solfrizzi, V. (Bari); Logroscino, G. (Bari/Tricase)
Randomized Trials in Developing Countries: Different Priorities and Study Design?
Marin, B.; Agbota, G.C.; Preux, P.-M.; Boumédiene, F. (Limoges)
The Right Therapy for Neurological Disorders: From Randomized Trials to Clinical Practice - Patients versus Investigator Expectations and Needs
Bruijn, L.I. (Washington, D.C.); Kolb, S. (Norfolk, Va.)
General Overview, Conclusions, and Future Directions
Beghi, E. (Milan); Logroscino, G. (Bari/Tricase)
Author Index
Subject Index
Foreword
The right therapy needs to be evidence based for neurological disorders just like all the diseases that afflict humankind. Evidence-based medicine requires randomized clinical trials (RCTs) to establish the efficacy and effectiveness of therapeutic interventions. RCTs, today mostly focused on drug evaluation, need to be extended to other treatments too, such as medical devices, electrical stimulation, surgery, nutrition, and rehabilitation practices. Moreover, many current therapeutic practices are still largely based on tradition and impressions, not on evidence. Even when a treatment is based on RCTs, frequently too few patients are enrolled and there may be biases that undermine the significance of the results.
This all reflects the vast economic interests that today surround medicine as a whole, and obviously also neurology. RCTs need to be conducted by independent organizations that may offer advantages over trials run by industry.
It may be worth very briefly mentioning the principal bias that is frequently detected. Selection of the population is certainly one of the main problems because it is very hard to balance the need for a homogeneous group of patients while at the same time covering patients likely to be encountered in current clinical practice. This usually results in an important imbalance concerning age and sex. Today almost 70% of drugs are used by patients older than 65; however, this population is underrepresented in most RCTs. These patients are no longer likely to have only a single disease, but because of their age they present polymorbidity and require polytherapy. These conditions are far removed from the clear situation of the RCT usually carried out in middle-aged males.
Females are also underrepresented in clinical trials and even when they are present it is difficult to find out from the trial publications whether they were even affected by the intervention similarly or differently from males.
The abuse of placebo is also very frequent in contrast with the ethical Declaration of Helsinki which requires comparisons with the best available treatment to avoid patients risking undue progression of their disease. Unfortunately, the approval of new drugs does not require comparative studies. In fact, the European directive specifies three requirements: quality, efficacy, and safety, but it does not require 'added therapeutic value'. If it did, drugs would be better selected. A consequence of the fact that the European directive does not require superiority is that RCTs often set out to prove only 'noninferiority', which is ethically unacceptable because the null hypothesis is that the tested drug or treatment is worse than the treatment already available. Usually, it is promised that the noninferior efficacy is compensated by other advantages such as less toxicity. However, RCTs are mainly designed to establish benefits while adverse reactions can be detected only in clinical practice once the treatment has been available for several years.
Clinical interventions must offer an outcome that is beneficial for patients, but RCTs often employ surrogate end points which are not always relevant to the patients' quality of life. A typical case is a drug that reduces the v